Oral care compositions comprising chlorite and methods

ABSTRACT

The present invention relates to oral care compositions, including therapeutic rinses, especially mouth rinses, as well as toothpastes, gels, tooth powders, chewing gums, mouth sprays, and lozenges (including breath mints), comprising at least a minimally effective amount of chlorite ion, wherein preferably the pH of the final composition is greater than 7 and level of chlorine dioxide or chlorous acid is less than about 50 ppm, preferably is essentially free of chlorine dioxide or chlorous acid. This invention further relates to a method for treating or preventing gingivitis, plaque, periodontal disease, and/or breath malodor, and/or for the whitening of teeth, in humans or other animals, by applying a safe and effective amount of the chlorite ion composition to the oral cavity.

This application is a divisional of U.S. patent application No.09/032,234, filed Feb. 27, 1998, now U.S. Pat. No. 6,132,702, issuedOct. 17, 2000.

TECHNICAL FIELD

The present invention relates to oral care compositions, includingtherapeutic rinses, especially mouth rinses, as well as toothpastes,tooth gels, tooth powders, chewing gums, mouth sprays, and lozenges(including breath mints), comprising an effective amount of chloriteion. This invention further relates to a method for treating orpreventing conditions of the oral cavity, such as gingivitis, plaque,periodontal disease, and/or breath malodor, as well as to a method forwhitening teeth, in humans or other animals.

BACKGROUND ART

Oral malodor, plaque, gingivitis, periodontal disease, and discolorationof the teeth, are all undesirable conditions that affect many people.First malodor of the oral cavity is also known as halitosis or badbreath. It is broadly estimated in the U.S. that 20-90 millionindividuals have oral malodor. It is generally believed that the causeof this condition is due to the presence of anaerobic bacteria,especially gram-negative anaerobic bacteria, in the mouth. Thesebacteria will generate volatile sulfur compounds (VSC) which are knownto cause breath malodor.

It is recognized in the art that some breath malodor is caused by threechemical compounds. Specifically, these compounds are hydrogen sulfide(H—S—H), methyl mercaptan (CH₃—S—H) and dimethyl sulfide (CH₂—S—CH₃).These compounds result from the degradation of epithelial cells andbacteria in the oral cavity. Specifically, the polypeptide chains of theepithelial cell walls, are composed of a series of amino acids includingcysteine and methionine which contain sulfur side chains. The death ofmicroorganisms or epithelial cells results in degradation of thepolypeptide chains into their amino acid components, especially cysteineand methionine. Cysteine and methionine are precursors to the formationof VSC.

It is also recognized in the art that oral malodor not only comes fromthe posterior dorsal surface of the tongue but also from periodontalpockets. Furthermore, a person with gingivitis or periodontal diseasemay have increased oral malodor from disintegrated epithelial cells.Epithelial cells turn over faster if inflammation is present. Therefore,a larger number of these dead epithelial cells remain in the oral cavityand will degrade into the malodorous compounds.

In addition VSC will also alter the epithelial barrier, permittingpenetration of the barrier by antigenic substances. For example, VSCsuch as hydrogen sulfide, methyl mercaptan and dimethyl sulfidecontribute to the penetration of bacterial toxins through the epithelialbarrier into the underlying basal lamina and connective tissue. A.Rizzo, Peridontics, 5: 233-236 (1967); W. Ng and J. Tonzetich, J. DentalResearch, 63(7): 994-997 (1984); M. C. Solis-Gaffar, T. J. Fischer andA. Gaffar, J. Soc. Cosmetic Chem., 30: 241-247 (1979). Thereafter,bacterial toxins, bacteria and virus can invade the underlying gingivaltissue adjacent to the sulcular space, thereafter invading theunderlying connective tissue. A decrease in VSC will decrease the tissuepermeability to oral toxins and bacteria.

Systemic entities can contribute to oral malodor as well. These entitiesinclude oral carcinomas, diabetes, liver and kidney abnormalities,medications which change the oral environment, ENT problems such aschronic sinusitis, tonsillitis and inflamed adenoids. Gastrointestinalproblems do not contribute to chronic oral malodor, although this is acommon belief. Evaluation and diagnosis of oral malodor can be achievedwith the Halimeter (Interscan). The Halimeter is a gas-analysis sensorthat measures the volatile sulfur compounds in breath.

Furthermore, periodontal disease is also an undesirable condition whichhas widespread occurrence. Periodontal disease is a major cause of toothloss in adults, beginning as early as age 12. Even by age 15, it ispossible that 4 out of 5 persons already have gingivitis and possibly asmany as 4 out of 10 have periodontitis.

Periodontal disease affects the periodontum, which is the investing andsupporting tissues surrounding a tooth (i.e., the periodontal ligament,the gingiva, and the alveolar bone). Gingivitis and periodontitis areinflammatory disorders of the gingiva and the deeper periodontaltissues, respectively.

It is well accepted that periodontal disease is associated with theaccumulation of plaque on the teeth. The teeth are coated with asalivary proteanaceous material (pellicle) and thereafter streptococciadhere to this coating. Gingivitis occurs from the dental plaque, andperiodontitis is caused by the infection spreading to the periodontalpocket or space between the gingiva and the tooth root.

Furthermore, consumers are very interested in making their teeth whiter.Consumers consider people with whiter teeth as having more personalconfidence and better social acceptance.

Teeth comprise both an inner dentin layer and an outer hard enamellayer. The enamel layer protects the inner dentin layer and live tissueand serves as the contact surface for mastication of solid food. Theenamel layer is generally translucent and slightly off-white in color.It is also considered porous since the hydroxy apatite crystals thatcomprise the enamel form microscopic hexagonal rods or prisms havingmicroscopic pores or channels between them. As a result of this porousstructure, staining agents and discoloring substances, such asantibiotics, foods containing coloring materials, coffee, cola, tea,tabacco, etc., can permeate the enamel and change its surface to appearyellow or brownish in color.

While good oral hygiene, as achieved by brushing the teeth with acleansing dentifrice, may help reduce the incidence of stain,gingivitis, plaque, periodontal disease, and/or breath malodor, it doesnot necessarily prevent or eliminate their occurrence. Microorganismscontribute to both the initiation and progression of gingivitis, plaque,periodontal disease, and/or breath malodor. Thus, in order to prevent ortreat these conditions, these microorganisms must be suppressed by somemeans other than simple mechanical scrubbing. In addition, simplemechanical scrubbing will not be entirely effective to remove all staintypes and/or whiten the teeth.

Towards this end, a great deal of research has been aimed at developingtherapeutic compositions and methods of treating the above conditions,that are effective in suppressing microorganisms. Also, research hasbeen aimed at developing effective whitening compositions. Some of thisresearch has focused on oral care compositions and methods comprisingchlorine dioxide or chlorine dioxide generating compounds. Chlorinedioxide is a very strong oxidant and is known as a broad spectrumantimicrobial agent.

The prior art discloses compositions and methods that use chlorinedioxide for the treatment of various oral care conditions. Most of theseprior art references teach that the delivery of chlorine dioxide isessential to provide efficacy. This is in contrast to the presentinvention which focuses on the delivery of chlorite ion to the oralcavity, to provide efficacy. The compositions and methods of the presentinvention are specifically and intentionally designed to avoid orminimize the production of chlorine dioxide in the compositions.

The prior art teaches a variety of ways to deliver chlorine dioxide, inoral care compositions, to the oral cavity. For example, U.S. Pat. Nos.4,689,215 issued Aug. 25, 1987; 4,837,009 issued Jun. 6, 1989;4,696,811, issued Sep. 29, 1987; 4,808,389 issued Feb. 28, 1989;4,786,492 issued Nov. 22, 1988; 4,788,053 issued Nov. 29, 1988;4,792,442 issued Dec. 20, 1988; 4,818,519 issued Apr. 4, 1989; 4,851,21issued Jul. 25, 1989; 4,855,135 issued Aug. 8, 1989; 4,793,989 issuedDec. 27, 1988; 4,886,657 issued Dec. 12, 1989; 4,889,714 issued Dec. 26,1989; 4,925,656 issued May 15, 1990; 4,975,285 issued Dec. 4, 1990;4,978,535 issued Dec. 18, 1990; 5,200,171 issued Apr. 6, 1993; 5,348,734issued Sep. 20, 1994; 5,618,550 issued Apr. 8, 1997, and 5,489,435issued Feb. 6, 1996, all to Perry A. Ratcliffe, teach oral carecompositions and methods of treatment using stabilized chlorine dioxide.

Additional prior art references, which teach the generation and deliveryof chlorine dioxide with activator compounds such as protic acids,reducing sugar activators, etc., include: U.S. Pat. Nos. 5,281,412,Lukacovic et al., issued Jan. 25, 1994, The Procter & Gamble Co.;5,110,652, Kross et al., issued Mar. 31, 1992, Alcide Corporation;5,019,402, Kross et al., issued May 28, 1991, Alcide; 4,986,990,Davidson et al., issued Jan. 22, 1991, Alcide; 4,891,216, Kross et al.,issued Jan. 2, 1990, Alcide; 4,330,531, Alliger, issued May 18, 1982; DE2,329,753, published Dec. 13, 1973, National Patent Development Corp.;EP 287,074, Kross et al., published Oct. 19, 1988, Alcide; EP 565,134,Kross et al., published Oct. 13, 1993, Alcide; and WO/95/27472, Richter,published Oct. 19, 1995.

Additional prior art references relating to chlorine dioxidecompositions include: GB 2,289,841, Mehmet, published Jun. 12, 1995,Janina International; GB 2,290,233, Drayson et al., published Dec. 20,1995, Medical Express Limited; WO 96/25916, Van Den Bosch et al.,published Aug. 29, 1996, Diamond White; JP 054,311, Tsuchikura,published Mar. 28, 1985; JP 105,610, Tsuchikura, published Jun. 11,1985; and WO/89/03179, Partlow et al., published Apr. 20, 1989, NewGeneration Products. All of the above references are incorporated hereinby reference in their entirety.

The above prior art references have not recognized that the delivery ofchlorite ion, itself, to the oral cavity will provide efficacy invarious oral care conditions. Because prior art references have focusedon the delivery of chlorine dioxide for efficacy, prior art compositionsand methods of treatment may have various drawbacks. For example,compositions comprising chlorine dioxide can exhibit aestheticdisadvantages such as “chlorine” (e.g. swimming pool) taste and smell.In addition due to the strong oxidizing capability of chlorine dioxide,compositions comprising chlorine dioxide may have certain stabilitydisadvantages, especially in oral care formulations.

Therefore, prior art compositions, mentioned above, have not beenentirely satisfactory for the treatment and/or prevention of gingivitis,plaque, periodontal disease, and/or breath malodor or for the whiteningof teeth. Therefore, additional efficacious compositions and methods oftreatment for these purposes are desirable.

As mentioned above, the present invention relates to the delivery ofchlorite ion to the oral cavity for efficacy. The present invention isspecifically designed to avoid or minimize the production of chlorinedioxide or chlorous acid in the compositions. The present invention,therefore, relates to oral care compositions comprising chlorite ionwherein no (or only very low levels of) chlorine dioxide or chlorousacid is generated or is present in the oral care compositions at thetime of use. Moreover, the present invention preferably relates to oralcare compositions comprising chlorite ion with relatively alkaline pHs,e.g. at pHs above 7, whereby no (or only very low levels of) chlorinedioxide or chlorous acid is generated or is present in the oral carecomposition at the time of use. Further, compositions of the presentinvention comprise at least a minimum amount of chlorite ion foreffectiveness. These compositions and methods (of the present invention)are effective even though no (or only very low levels of) chlorinedioxide or chlorous acid is generated or is present in thesecompositions.

It is the purpose of the present invention to provide compositions andmethods for treating or preventing diseases of the oral cavity, such asplaque, gingivitis, periodontal disease, and for treating or preventingother conditions such as breath malodor, in humans or other animals, byutilizing an effective amount of chlorite ion wherein no (or only verylow levels of) chlorine dioxide or chlorous acid is generated or ispresent in the oral care composition at the time of use. The pH of thefinal composition is preferably alkaline, e.g. above pH 7.

It is also the purpose of the present invention to provide compositionsand methods to whiten teeth, in humans or other animals, by utilizing aneffective amount of chlorite ion wherein no (or only very low levels of)chlorine dioxide or chlorous acid is generated or is present in the oralcare composition at the time of use. The pH of the final composition ispreferably alkaline, e.g. above pH 7.

Further, the present invention relates to oral care compositions,including therapeutic rinses, especially mouth rinses, as well astoothpastes, tooth gels, tooth powders, non-abrasive gels, chewing gums,mouth sprays, and lozenges (including breath mints). These compositionscomprise a minimally effective amount of chlorite ion.

These compositions are effective in killing, and/or altering thebacterial metabolism, and/or for a period of time suppressing the growthof, microorganisms which cause topically-treatable infections anddiseases of the oral cavity, such as plaque, gingivitis, periodontaldisease, and breath malodor. These compositions are also effective towhiten teeth.

SUMMARY OF THE INVENTION

The present invention relates to oral care compositions, includingtherapeutic rinses, especially mouth rinses, as well as toothpastes,tooth gels, tooth powders, non-abrasive gels, chewing gums, mouthsprays, and lozenges (including breath mints), comprising:

(a) a safe and effective amount, preferably a minimally effectiveamount, of chlorite ion; and

(b) a pharmaceutically-acceptable topical, oral carrier; wherein thelevel of chlorine dioxide or chlorous acid in the final composition isless than about 50 ppm; and preferably the pH of the final compositionis greater than 7. More preferably the pH of the composition is greaterthan 7.6, even more preferably greater than 8.

This invention further relates to a method for treating or preventingdiseases of the oral cavity, such as gingivitis, plaque, periodontaldisease, and/or breath malodor, and/or for the whitening of teeth, inhumans or other animals, by applying the above compositions to the oralcavity and/or teeth.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to compositions and methods of treating orpreventing diseases of the oral cavity (e.g. plaque, gingivitis,periodontal disease), breath malodor, and for whitening teeth, in humansor other animals, by topically applying to the oral cavity, a safe andeffective amount of chlorite ion.

By “diseases or conditions of the oral cavity,” as used herein, is meantdiseases of the oral cavity including periodontal disease, gingivitis,periodontitis, periodontosis, adult and juvenile periodontitis, andother inflammatory conditions of the tissues within the oral cavity,plus caries, necrotizing ulcerative gingivitis, and other conditionssuch as oral or breath malodor. Also specifically included aredentoalveolar infections, dental abscesses (e.g., cellulitis of the jaw;osteomyelitis of the jaw), acute necrotizing ulcerative gingivitis(i.e., Vincent's infection), infectious stomatitis (i.e., acuteinflammation of the buccal mucosa), and Noma (i.e., gangrenousstomatitis or cancrum oris). Oral and dental infections are more fullydisclosed in Finegold, Anaerobic Bacteria in Human Diseases, chapter 4,pp 78-104, and chapter 6, pp 115-154 (Academic Press, Inc., NY, 1977),the disclosures of which are incorporated herein by reference in theirentirety. The compositions and methods of treatment of the presentinvention are particularly effective for treating or preventingperiodontal disease (gingivitis and/or periodontitis) and breathmalodor.

By “safe and effective amount” as used herein is meant an amount of achlorite ion, high enough to significantly (positively) modify thecondition to be treated or to effect the desired whitening result, butlow enough to avoid serious side effects (at a reasonable benefit/riskratio), within the scope of sound medical/dental judgment. The safe andeffective amount of a chlorite ion, will vary with the particularcondition (e.g., to effect whitening, to treat disease of the oralcavity or malodor) being treated, the age and physical condition of thepatient being treated, the severity of the condition, the duration oftreatment, the nature of concurrent therapy, the specific form (i.e.,salt) of the chlorite source employed, and the particular vehicle fromwhich the chlorite ion is applied.

By “toothpaste” as used herein is meant paste, powder, and tooth gelformulations unless otherwise specified.

By “oral care composition” or “oral composition” as used herein is meanta product which is not intentionally swallowed for purposes of systemicadministration of therapeutic agents, but is retained in the oral cavityfor a sufficient time to contact substantially all of the dentalsurfaces and/or oral mucosal tissues for purposes of oral activity.

By “essentially free of chlorous acid or chlorine dioxide” as usedherein is meant a composition which comprises very low levels, e.g. lessthan about 5 ppm, preferably less than about 1 ppm of chlorine dioxideor chlorous acid, using known analytical methods for measuring chlorinedioxide or chlorous acid as disclosed hereinafter.

Chlorite Ion Source

The present invention includes chlorite ion as an essential ingredientin the compositions and methods of the present invention. The chloriteion can come from any type of chlorite salt. Examples include alkalimetal chlorites, alkaline earth metal chlorites, and any othertransition metals, inner transition metal chlorites and/or polymericsalts. Water soluble chlorite salts are preferred. Examples of suitablemetal chlorites include calcium chlorite, barium chlorite, magnesiumchlorite, lithium chlorite, sodium chlorite and potassium chlorite.Sodium chlorite and potassium chlorite are preferred. Sodium chlorite isparticularly preferred. Mixtures of two or more sources of chlorite mayalso be used.

While not intending to be bound by theory, the present inventors believethat chlorite ion provides antimicrobial activity, especiallyselectivity for gram negative anaerobes, for oral care compositions.

For dentifrice compositions of the present invention, the level ofchlorite ion is greater than about 0.02%, preferably greater than about0.4%, more preferably greater than about 0.56%, even more preferablygreater than about 0.75%, and even more preferably greater than about1%, by weight of the composition. The composition preferably comprisesabout 2% by weight of the composition, of chlorite ion.

For mouthrinse compositions of the present invention, the level ofchlorite ion is greater than about 0.04%, preferably greater than about0.075%, more preferably greater than about 0.15%, by weight of thecomposition.

For lozenge or breath mint compositions of the present invention, theamount of chlorite ion is from about 0.1 mg to about 12 mg, preferablyfrom about 1 mg to about 6 mg, per unit.

For gum compositions of the present invention, the amount of chloriteion is from about 0.1 mg to about 12 mg, preferably from about 1 mg toabout 6 mg, per unit.

For methods of treating or preventing gingivitis or for whitening theteeth, preferably the compositions comprise from about 0.75% to about6%, of chlorite ion, by weight of the composition.

In the context of breath odor elimination or reduction, the compositionsand methods of the present invention provide long-lasting breathprotection, e.g. greater than about 3 hours.

For methods of treating or preventing oral malodor, and for breathprotection lasting greater than about 3 hours, preferably thecompositions comprise from about 0.04% to about 6%, of chlorite ion, byweight of the composition.

Chlorite salts are available from various suppliers as sodium chlorite.Sodium chlorite is commercially available as a technical grade powder orflake, and as an aqueous liquid concentrate in a range ofconcentrations. Example of sources of sodium chlorite include: sodiumchlorite available from Aragonesas and from Vulcan. These sourcesgenerally have no more than 4% sodium chlorate as well. Preferably theratio of chlorite to chlorate is greater than 8:1 and generally about20:1.

Preferably, the source of chlorite ion has high purity, e.g. 70% orgreater. Furthermore, preferably the compositions of the presentinvention are essentially free of hypochlorite metal salt orhypochlorite ion, dichloroisocyanurate, or salts thereof.

Preferably, the level of chlorite ion is measured by gradient separationof inorganic and organic acid anions using Ion Pac ASII exchange column,available from Dionex Corporation, Sunnyvale, Calif.

The final compositions of the present invention preferably comprise lowlevels of chlorine dioxide or chlorous acid, or are essentially free ofchlorine dioxide or chlorous acid (have less than about 5 ppm,preferably less than about 1 ppm of chlorine dioxide or chlorous acid).

For mouthwash and dentifrice compositions the level of chlorine dioxideor chlorous acid in the final composition is preferably less than about50 ppm, more preferably less than about 25 ppm, and even more preferablyless than about 10 ppm.

For dual phase compositions the level of chlorine dioxide or chlorousacid is measured within about 2 to 3 minutes after the two phases aremixed together.

Analytical methods to measure the levels of chlorine dioxide or chlorousacid in the compositions of the present invention are known in the art.For example, L. S. Clesceri, A. E. Greenberg, and R. R. Trussel,Standard Methods for the Examination of Water and Wastewater, 17^(th)ed., American Public Health Association, Washington, D.C., 1989, pp.4-75 through 4-83; E. M. Aieta, P. V. Roberts, and M. Hernandez, J. Am.Water Works Assoc. 76(1), pp. 64-70 (1984); J. D. Pfaff and C. A.Brockhoff, J. Am. Water Works Assoc. 82(4), pp. 192-195 (1990); G.Gordon, W. J. Cooper, R. G. Rice, and G. E. Pacey, J. Am. Water WorksAssoc. 80(9), pp. 94-108 (1988); D. L. Harp, R. L. Klein, and D. J.Schoonover, J. Am. Water Works Assoc. 73(7), pp. 387-389 (1981); G.Gordon, W. J. Cooper, R. G. Rice, and G. E. Pacey, Am. Water WorksAssoc. Res. Foundation, Denver, Colo., 1987, pp. 815. All of thesereferences are herein incorporated by reference in their entirety.

The pH of the final composition (either a single phase or dual phasecomposition) of the present invention is greater than 7, preferablygreater than 7.6, more preferably greater than 8. Preferably the pH ofthe final composition is from 8 to 12, more preferably the pH is 10.

Preferably for mouthwash compositions the pH of the final composition isgreater than 7.5, preferably greater than 8. Preferably the pH of thefinal composition is from 8 to 12, more preferably the pH is 10.

Preferably for dentifrice compositions the pH of the final compositionis greater than 7.6, preferably greater than 8, more preferably greaterthan 9. Preferably the pH of the final composition is from 8 to 12, morepreferably the pH is 10.

For dual phase compositions the pH is measured after the two phases aremixed together, and is not based on the pH of a single phase prior tomixing.

The pH of the final dentifrice composition is measured from a 3:1aqueous slurry of toothpaste, e.g. 3 parts water to 1 part toothpaste.

Pharmaceutically-Acceptable Excipients

By “pharmaceutically-acceptable excipient” or“pharmaceutically-acceptable oral carrier,” as used herein, is meant oneor more compatible solid or liquid filler diluents or encapsulatingsubstances which are suitable for topical, oral administration. By“compatible,” as used herein, is meant that the components of thecomposition are capable of being commingled without interaction in amanner which would substantially reduce the composition's stabilityand/or efficacy for treating or preventing breath malodor, plaque,gingivitis, periodontal disease and to whiten the teeth, according tothe compositions and methods of the present invention.

The carriers or excipients of the present invention can include theusual and conventional components of toothpastes (including gels andgels for subgingival application), mouth rinses, mouth sprays, chewinggums, and lozenges (including breath mints) as more fully describedhereinafter.

The compositions of the present invention can be dual phase compositionsor single phase compositions. The chlorite ion, however, is relativelyreactive and will react with certain carriers or excipients generallyused in oral care compositions. Therefore, based on this reactivity, thepreferred compositions of the present invention are dual phasecompositions. These compositions comprise a first phase and a secondphase:

(a) the first phase comprising chlorite ion; and

(b) the second phase comprising a pharmaceutically-acceptable topical,oral carrier and comprising no chlorite.

These dual phase compositions comprise two phases, wherein chlorite ionis placed in a first phase which is to be kept separate from the secondphase. The first phase comprising chlorite ion can additionally comprisepharmaceutically-acceptable topical, oral carriers which are compatiblewith chlorite ion. Preferably the first phase, in addition to chlorite,comprises one (or more) compatible binder, humectant, buffer and/orpreservative. Preferably, the second phase, which comprises no chlorite,comprises flavorant, surfactant, fluoride ion, and/or abrasive.

Normally, each phase in these two phase compositions, is in a separatecontainer or in a single container with two chambers. Prior to use ofdual phase composition by the consumer, the two phases are combined bycoextrusion of the two separate phases, preferably at a 1:1 volume tovolume ratio, and the composition is preferably used immediately afterpreparation, i.e. within about 5 minutes.

The two phases, however, can be combined from about 1 minute to about 1hour before use, or during the use of the composition.

Dual phase containers are disclosed in U.S. Pat. Nos. 5,052,590,Ratcliffe, issued Oct. 1, 1991 and 4,330,531, Alliger, issued May 18,1982.

In another preferred embodiment, chlorite is substantially anhydrousuntil just prior to use. For example, preparing a mouth rinse solutionjust prior to use by dissolving in water, a substantially anhydrousconcentrate of chlorite, to the necessary concentration for use in themethod of treatments of the present invention.

The choice of a carrier to be used is basically determined by the waythe composition is to be introduced into the oral cavity. If atoothpaste (including tooth gels, etc.) is to be used, then a“toothpaste carrier” is chosen as disclosed in, e.g., U.S. Pat. No.3,988,433, to Benedict, the disclosure of which is incorporated hereinby reference (e.g., abrasive materials, sudsing agents, binders,humectants, flavoring and sweetening agents, etc.). If a mouth rinse isto be used, then a “mouth rinse carrier” is chosen, as disclosed in,e.g., U.S. Pat. No. 3,988,433 to Benedict (e.g., water, flavoring andsweetening agents, etc.). Similarly, if a mouth spray is to be used,then a “mouth spray carrier” is chosen or if a lozenge is to be used,then a “lozenge carrier” is chosen (e.g., a candy base), candy basesbeing disclosed in, e.g., U.S. Pat. No. 4,083,955, to Grabenstetter etal., which is incorporated herein by reference; if a chewing gum is tobe used, then a “chewing gum carrier” is chosen, as disclosed in, e.g.,U.S. Pat. No. 4,083,955, to Grabenstetter et al., which is incorporatedherein by reference (e.g., gum base, flavoring and sweetening agents).If a sachet is to be used, then a “sachet carrier” is chosen (e.g.,sachet bag, flavoring and sweetening agents). If a subgingival gel is tobe used (for delivery of actives into the periodontal pockets or aroundthe periodontal pockets), then a “subgingival gel carrier” is chosen asdisclosed in, e.g. U.S. Pat. Nos. 5,198,220, Damani, issued Mar. 30,1993, P&G, 5,242,910, Damani, issued Sep. 7, 1993, P&G, all of which areincorporated herein by reference. Carriers suitable for the preparationof compositions of the present invention are well known in the art.Their selection will depend on secondary considerations like taste,cost, and shelf stability, etc.

Preferred compositions of the subject invention are in the form ofdentifrices, such as toothpastes, tooth gels and tooth powders.Components of such toothpaste and tooth gels generally include one ormore of a dental abrasive (from about 10% to about 50%), a surfactant(from about 0.5% to about 10%), a thickening agent (from about 0.1% toabout 5%), a humectant (from about 10% to about 55%), a flavoring agent(from about 0.04% to about 2%), a sweetening agent (from about 0.1% toabout 3%), a coloring agent (from about 0.01% to about 0.5%) and water(from about 2% to about 45%). Such toothpaste or tooth gel may alsoinclude one or more of an anticaries agent (from about 0.05% to about0.3% as fluoride ion), and an anticalculus agent (from about 0.1% toabout 13%). Tooth powders, of course, contain substantially allnon-liquid components.

Other preferred compositions of the present invention are non-abrasivegels, including subgingival gels, which generally include a thickeningagent (from about 0.1% to about 20%), a humectant (from about 10% toabout 55%), a flavoring agent (from about 0.04% to about 2%), asweetening agent (from about 0.1% to about 3%), a coloring agent (fromabout 0.01% to about 0.5%), water (from about 2% to about 45%), and maycomprise an anticaries agent (from about 0.05% to about 0.3% as fluorideion), and an anticalculus agent (from about 0.1% to about 13%).

Other preferred compositions of the subject invention are mouthwashes,including mouth sprays. Components of such mouthwashes and mouth spraystypically include one or more of water (from about 45% to about 95%),ethanol (from about 0% to about 25%), a humectant (from about 0% toabout 50%), a surfactant (from about 0.01% to about 7%), a flavoringagent (from about 0.04% to about 2%), a sweetening agent (from about0.1% to about 3%), and a coloring agent (from about 0.001% to about0.5%). Such mouthwashes and mouth sprays may also include one or more ofan anticaries agent (from about 0.05% to about 0.3% as fluoride ion),and an anticalculus agent (from about 0.1% to about 3%).

Other preferred compositions of the subject invention are dentalsolutions. Components of such dental solutions generally include one ormore of water (from about 90% to about 99%), preservative (from about0.01% to about 0.5%), thickening agent (from 0% to about 5%), flavoringagent (from about 0.04% to about 2%), sweetening agent (from about 0.1%to about 3%), and surfactant (from 0% to about 5%).

Chewing gum compositions typically include one or more of a gum base(from about 50% to about 99%), a flavoring agent (from about 0.4% toabout 2%) and a sweetening agent (from about 0.01% to about 20%).

The term “lozenge” as used herein includes: breath mints, troches,pastilles, microcapsules, and fast-dissolving solid forms includingfreeze dried forms (cakes, wafers, thin films, tablets) andfast-dissolving solid forms including compressed tablets. The term“fast-dissolving solid form” as used herein means that the solid dosageform dissolves in less than about 60 seconds, preferably less than about15 seconds, more preferably less than about 5 seconds, after placing thesolid dosage form in the oral cavity. Fast-dissolving solid forms aredisclosed in copending U.S. patent application Ser. No. 08/253,890,filed Jun. 3, 1994, Brideau; U.S. Pat. Nos. 4,642,903; 4,946,684;4,305,502; 4,371,516; 5,188,825; 5,215,756; 5,298,261; 3,882,228;4,687,662; 4,642,903. All of these patents are incorporated herein byreference in their entirety.

Lozenges include discoid-shaped solids comprising a therapeutic agent ina flavored base. The base may be a hard sugar candy, glycerinatedgelatin or combination of sugar with sufficient mucilage to give itform. These dosage forms are generally described in Remington: TheScience and Practice of Pharmacy, 19^(th) Ed., Vol. II, Chapter 92,1995. Lozenge compositions (compressed tablet type) typically includeone or more fillers (compressible sugar), flavoring agents, andlubricants. Microcapsules of the type contemplated herein are disclosedin U.S. Pat. No. 5,370,864, Peterson et al., issued Dec. 6, 1994, whichis herein incorporated by reference in its entirety.

The compositions of the present invention are preferably essentiallyfree of organic solvents. The compositions of the present invention arealso preferably essentially free of peroxy compounds.

Types of carriers or oral care excipients which may be included incompositions of the present invention, along with specific non-limitingexamples, are:

Abrasives

Dental abrasives useful in the topical, oral carriers of thecompositions of the subject invention include many different materials.The material selected must be one which is compatible within thecomposition of interest and does not excessively abrade dentin. Suitableabrasives include, for example, silicas including gels and precipitates,insoluble sodium polymetaphosphate, hydrated alumina, calcium carbonate,dicalcium orthophosphate dihydrate, calcium pyrophosphate, tricalciumphosphate, calcium polymetaphosphate, and resinous abrasive materialssuch as particulate condensation products of urea and formaldehyde.

Another class of abrasives for use in the present compositions is theparticulate thermo-setting polymerized resins as described in U.S. Pat.No. 3,070,510 issued to Cooley & Grabenstetter on Dec. 25, 1962.Suitable resins include, for example, melamines, phenolics, ureas,melamine-ureas, melamine-formaldehydes, urea-formaldehyde,melamine-urea-formaldehydes, cross-linked epoxides, and cross-linkedpolyesters. Mixtures of abrasives may also be used.

Silica dental abrasives of various types are preferred because of theirunique benefits of exceptional dental cleaning and polishing performancewithout unduly abrading tooth enamel or dentine. The silica abrasivepolishing materials herein, as well as other abrasives, generally havean average particle size ranging between about 0.1 to about 30 microns,and preferably from about 5 to about 15 microns. The abrasive can beprecipitated silica or silica gels such as the silica xerogels describedin Pader et al., U.S. Pat. No. 3,538,230, issued Mar. 2, 1970, andDiGiulio, U.S. Pat. No. 3,862,307, issued Jan. 21, 1975, bothincorporated herein by reference. Preferred are the silica xerogelsmarketed under the trade name “Syloid” by the W.R. Grace & Company,Davison Chemical Division. Also preferred are the precipitated silicamaterials such as those marketed by the J. M. Huber Corporation underthe trade name, Zeodent®, particularly the silica carrying thedesignation Zeodent 119.® The types of silica dental abrasives useful inthe toothpastes of the present invention are described in more detail inWason, U.S. Pat. No. 4,340,583, issued Jul. 29, 1982. The abrasive inthe toothpaste compositions described herein is generally present at alevel of from about 6% to about 70% by weight of the composition.Preferably, toothpastes contain from about 10% to about 50% of abrasive,by weight of the composition.

A particularly preferred precipitated silica is the silica disclosed inU.S. Pat. Nos. 5,603,920, issued on Feb. 18, 1997; 5,589,160, issuedDec. 31, 1996; 5,658,553, issued Aug. 19, 1997; 5,651,958, issued Jul.29, 1997, all of which are assigned to the Procter & Gamble Co. All ofthese patents are incorporated herein by reference in their entirety.

Mixtures of abrasives can be used. All of the above patents regardingdental abrasives are incorporated herein by reference. The total amountof abrasive in dentifrice compositions of the subject inventionpreferably range from about 6% to about 70% by weight; toothpastespreferably contain from about 10% to about 50% of abrasives, by weightof the composition. Solution, mouth spray, mouthwash and non-abrasivegel compositions of the subject invention typically contain no abrasive.

Sudsing Agents (Surfactants)

Suitable sudsing agents are those which are reasonably stable and formfoam throughout a wide pH range. Sudsing agents include nonionic,anionic, amphoteric, cationic, zwitterionic, synthetic detergents, andmixtures thereof. Many suitable nonionic and amphoteric surfactants aredisclosed by U.S. Pat. Nos. 3,988,433 to Benedict; U.S. Pat. No.4,051,234, issued Sep. 27, 1977, and many suitable nonionic surfactantsare disclosed by Agricola et al., U.S. Pat. No. 3,959,458, issued May25, 1976, both incorporated herein in their entirety by reference.

a.) Nonionic and Amphoteric Surfactants

Nonionic surfactants which can be used in the compositions of thepresent invention can be broadly defined as compounds produced by thecondensation of alkylene oxide groups hydrophilic in nature) with anorganic hydrophobic compound which may be aliphatic or alkyl-aromatic innature. Examples of suitable nonionic surfactants include poloxamers(sold under trade name Pluronic), polyoxyethylene sorbitan esters (soldunder trade name Tweens), fatty alcohol ethoxylates, polyethylene oxidecondensates of alkyl phenols, products derived from the condensation ofethylene oxide with the reaction product of propylene oxide and ethylenediamine, ethylene oxide condensates of aliphatic alcohols, long chaintertiary amine oxides, long chain tertiary phosphine oxides, long chaindialkyl sulfoxides, and mixtures of such materials.

The amphoteric surfactants useful in the present invention can bebroadly described as derivatives of aliphatic secondary and tertiaryamines in which the aliphatic radical can be a straight chain orbranched and wherein one of the aliphatic substituents contains fromabout 8 to about 18 carbon atoms and one contains an anionicwater-solubilizing group, e.g., carboxylate, sulfonate, sulfate,phosphate, or phosphonate. Other suitable amphoteric surfactants arebetaines, specifically cocamidopropyl betaine. Mixtures of amphotericsurfactants can also be employed.

The present composition can typically comprise a nonionic, amphoteric,or combination of nonionic and amphoteric surfactant each at a level offrom about 0.025% to about 5%, preferably from about 0.05% to about 4%,and most preferably from about 0.1% to about 3%.

b.) Anionic Surfactants

Anionic surfactants useful herein include the water-soluble salts ofalkyl sulfates having from 8 to 20 carbon atoms in the alkyl radical(e.g., sodium alkyl sulfate) and the water-soluble salts of sulfonatedmonoglycerides of fatty acids having from 8 to 20 carbon atoms. Sodiumlauryl sulfate and sodium coconut monoglyceride sulfonates are examplesof anionic surfactants of this type. Other suitable anionic surfactantsare sarcosinates, such as sodium lauroyl sarcosinate, taurates, sodiumlauryl sulfoacetate, sodium lauroyl isethionate, sodium laurethcarboxylate, and sodium dodecyl benzenesulfonate. Mixtures of anionicsurfactants can also be employed. The present composition typicallycomprises an anionic surfactant at a level of from about 0.025% to about9%, preferably from about 0.05% to about 7%, and most preferably fromabout 0.1% to about 5%.

Fluoride Ions

The present invention may also incorporate free fluoride ions. Preferredfree fluoride ions can be provided by sodium fluoride, stannousfluoride, indium fluoride, and sodium monofluorophosphate. Sodiumfluoride is the most preferred free fluoride ion. Norris et al., U.S.Pat. No. 2,946,725, issued Jul. 26, 1960, and Widder et al., U.S. Pat.3,678,154 issued Jul. 18, 1972, disclose such salts as well as others.These patents are incorporated herein by reference in their entirety.

The present composition may contain from about 50 ppm to about 3500 ppm,and preferably from about 500 ppm to about 3000 ppm of free fluorideions.

Thickening Agents

In preparing toothpaste or gels, it is necessary to add some thickeningmaterial to provide a desirable consistency of the composition, toprovide desirable chlorite release characteristics upon use, to provideshelf stability, and to provide stability of the composition, etc.Preferred thickening agents are carboxyvinyl polymers, carrageenan,hydroxyethyl cellulose, laponite and water soluble salts of celluloseethers such as sodium carboxymethylcellulose and sodium carboxymethylhydroxyethyl cellulose. Natural gums such as gum karaya, xanthan gum,gum arabic, and gum tragacanth can also be used. Colloidal magnesiumaluminum silicate or finely divided silica can be used as part of thethickening agent to further improve texture.

Some thickening agents, however, except polymeric polyether compounds,e.g., polyethylene or polypropylene oxide (M.W. 300 to 1,000,000),capped with alkyl or acyl groups containing 1 to about 18 carbon atoms,may react with chlorite. When chlorite is formulated separately in adual phase composition, preferred thickening agents are hydroxyethylcellulose and water-soluble salts of cellulose ethers such as sodiumcarboxymethyl cellulose and sodium carboxymethyl hydroxyethyl cellulose.

A preferred class of thickening or gelling agents includes a class ofhomopolymers of acrylic acid crosslinked with an alkyl ether ofpentaerythritol or an alkyl ether of sucrose, or carbomers. Carbomersare commercially available from B.F. Goodrich as the Carbopol® series.Particularly preferred carbopols include Carbopol 934, 940, 941, 956,and mixtures thereof.

Copolymers of lactide and glycolide monomers, the copolymer having themolecular weight in the range of from about 1,000 to about 120,000(number average), are useful for delivery of actives into theperiodontal pockets or around the periodontal pockets as a “subgingivalgel carrier.” These polymers are described in U.S. Pat. Nos. 5,198,220,Damani, issued Mar. 30, 1993, P&G, 5,242,910, Damani, issued Sep. 7,1993, P&G, and 4,443,430, Mattei, issued Apr. 17, 1984, all of which areincorporated herein by reference.

Thickening agents in an amount from about 0.1% to about 15%, preferablyfrom about 2% to about 10%, more preferably from about 4% to about 8%,by weight of the total toothpaste or gel composition, can be used.Higher concentrations can be used for chewing gums, lozenges (includingbreath mints), sachets, non-abrasive gels and subgingival gels.

Humectants

Another optional component of the topical, oral carriers of thecompositions of the subject invention is a humectant. The humectantserves to keep toothpaste compositions from hardening upon exposure toair, to give compositions a moist feel to the mouth, and, for particularhumectants, to impart desirable sweetness of flavor to toothpastecompositions. The humectant, on a pure humectant basis, generallycomprises from about 0% to about 70%, preferably from about 5% to about25%, by weight of the compositions herein. Suitable humectants for usein compositions of the subject invention include edible polyhydricalcohols such as glycerin, sorbitol, xylitol, butylene glycol,polyethylene glycol, and propylene glycol, especially sorbitol andglycerin.

Flavoring and Sweetening Agents

Flavoring agents can also be added to the compositions. Suitableflavoring agents include oil of wintergreen, oil of peppermint, oil ofspearmint, clove bud oil, menthol, anethole, methyl salicylate,eucalyptol, cassia, 1-menthyl acetate, sage, eugenol, parsley oil,oxanone, alpha-irisone, marjoram, lemon, orange, propenyl guaethol,cinnamon, vanillin, thymol, linalool, cinnamaldehyde glycerol acetalknown as CGA, and mixtures thereof. Flavoring agents are generally usedin the compositions at levels of from about 0.001% to about 5%, byweight of the composition.

Sweetening agents which can be used include sucrose, glucose, saccharin,dextrose, levulose, lactose, mannitol, sorbitol, fructose, maltose,xylitol, saccharin salts, thaumatin, aspartame, D-tryptophan,dihydrochalcones, acesulfame and cyclamate salts, especially sodiumcyclamate and sodium saccharin, and mixtures thereof. A compositionpreferably contains from about 0.1% to about 10% of these agents,preferably from about 0.1% to about 1%, by weight of the composition.

In addition to flavoring and sweetening agents, coolants, salivatingagents, warming agents, and numbing agents can be used as optionalingredients in compositions of the present invention. These agents arepresent in the compositions at a level of from about 0.001% to about10%, preferably from about 0.1% to about 1%, by weight of thecomposition.

The coolant can be any of a wide variety of materials. Included amongsuch materials are carboxamides, menthol, ketals, diols, and mixturesthereof. Preferred coolants in the present compositions are theparamenthan carboxyamide agents such as N-ethyl-p-menthan-3-carboxamide,known commercially as “WS-3”, N,2,3-trimethyl-2-isopropylbutanamide,known as “WS-23,” and mixtures thereof. Additional preferred coolantsare selected from the group consisting of menthol,3-1-menthoxypropane-1,2-diol known as TK-10 manufactured by Takasago,menthone glycerol acetal known as MGA manufactured by Haarmann andReimer, and menthyl lactate known as Frescolat® manufactured by Haarmannand Reimer. The terms menthol and menthyl as used herein include dextro-and levorotatory isomers of these compounds and racemic mixturesthereof. TK-10 is described in U.S. Pat. No. 4,459,425, Amano et al.,issued Jul. 10, 1984. WS-3 and other agents are described in U.S. Pat.No. 4,136,163, Watson, et al., issued Jan. 23, 1979; the disclosure ofboth are herein incorporated by reference in their entirety.

Preferred salivating agents of the present invention include Jambu®manufactured by Takasago. Preferred warming agents include capsicum andnicotinate esters, such as benzyl nicotinate. Preferred numbing agentsinclude benzocaine, lidocaine, clove bud oil, and ethanol.

Anticalculus Agent

The present invention also includes an anticalculus agent, preferably apyrophosphate ion source which is from a pyrophosphate salt. Thepyrophosphate salts useful in the present compositions include thedialkali metal pyrophosphate salts, tetraalkali metal pyrophosphatesalts, and mixtures thereof. Disodium dihydrogen pyrophosphate(Na₂H₂P₂O₇), tetrasodium pyrophosphate (Na₄P₂O₇), and tetrapotassiumpyrophosphate (K₄P₂O₇) in their unhydrated as well as hydrated forms arethe preferred species. In compositions of the present invention, thepyrophosphate salt may be present in one of three ways: predominatelydissolved, predominately undissolved, or a mixture of dissolved andundissolved pyrophosphate.

Compositions comprising predominately dissolved pyrophosphate refer tocompositions where at least one pyrophosphate ion source is in an amountsufficient to provide at least about 1.0% free pyrophosphate ions. Theamount of free pyrophosphate ions may be from about 1% to about 15%,preferably from about 1.5% to about 10%, and most preferably from about2% to about 6%. Free pyrophosphate ions may be present in a variety ofprotonated states depending on a the pH of the composition.

Compositions comprising predominately undissolved pyrophosphate refer tocompositions containing no more than about 20% of the totalpyrophosphate salt dissolved in the composition, preferably less thanabout 10% of the total pyrophosphate dissolved in the composition.Tetrasodium pyrophosphate salt is the preferred pyrophosphate salt inthese compositions. Tetrasodium pyrophosphate may be the anhydrous saltform or the decahydrate form, or any other species stable in solid formin the dentifrice compositions. The salt is in its solid particle form,which may be its crystalline and/or amorphous state, with the particlesize of the salt preferably being small enough to be aestheticallyacceptable and readily soluble during use. The amount of pyrophosphatesalt useful in making these compositions is any tartar control effectiveamount, and is generally from about 1.5% to about 15%, preferably fromabout 2% to about 10%, and most preferably from about 3% to about 8%, byweight of the dentifrice composition.

Compositions may also comprise a mixture of dissolved and undissolvedpyrophosphate salts. Any of the above mentioned pyrophosphate salts maybe used.

The pyrophosphate salts are described in more detail in Kirk & Othmer,Encyclopedia of Chemical Technology, Third Edition, Volume 17,Wiley-Interscience Publishers (1982), incorporated herein by referencein its entirety, including all references incorporated into Kirk &Othmer.

Optional agents to be used in place of or in combination with thepyrophosphate salt include such known materials as synthetic anionicpolymers, including polyacrylates and copolymers of maleic anhydride oracid and methyl vinyl ether (e.g., Gantrez), as described, for example,in U.S. Pat. No. 4,627,977, to Gaffar et al., the disclosure of which isincorporated herein by reference in its entirety; as well as, e.g.,polyamino propoane sulfonic acid (AMPS), zinc citrate trihydrate,polyphosphates (e.g., tripolyphosphate; hexametaphosphate),diphosphonates (e.g., EHDP; AHP), polypeptides (such as polyaspartic andpolyglutamic acids), and mixtures thereof.

Alkali Metal Bicarbonate Salt

The present invention may also include an alkali metal bicarbonate salt.Alkali metal bicarbonate salts are soluble in water and unlessstabilized, tend to release carbon dioxide in an aqueous system. Sodiumbicarbonate, also known as baking soda, is the preferred alkali metalbicarbonate salt. The present composition may contain from about 0.5% toabout 30%, preferably from about 0.5% to about 15%, and most preferablyfrom about 0.5% to about 5% of an alkali metal bicarbonate salt.

Miscellaneous Carriers

Water employed in the preparation of commercially suitable oralcompositions should preferably be of low ion content and free of organicimpurities. Water generally comprises from about 5% to about 70%, andpreferably from about 20% to about 50%, by weight of the compositionherein. These amounts of water include the free water which is addedplus that which is introduced with other materials, such as withsorbitol.

Titanium dioxide may also be added to the present composition. Titaniumdioxide is a white powder which adds opacity to the compositions.Titanium dioxide generally comprises from about 0.25% to about 5% byweight of the dentifrice compositions.

Antimicrobial antiplaque agents can also by optionally present in oralcompositions. Such agents may include, but are not limited to,triclosan, 5-chloro-2-(2,4-dichlorophenoxy)-phenol, as described in TheMerck Index, 11th ed. (1989), pp. 1529 (entry no. 9573) in U.S. Pat. No.3,506,720, and in European Patent Application No. 0,251,591 of BeechamGroup, PLC, published Jan. 7, 1988; chlorhexidine (Merck Index, no.2090), alexidine (Merck Index, no. 222; hexetidine (Merck Index, no.4624); sanguinarine (Merck Index, no. 8320); benzalkonium chloride(Merck Index, no. 1066); salicylanilide (Merck Index, no. 8299);domiphen bromide (Merck Index, no. 3411); cetylpyridinium chloride (CPC)(Merck Index, no. 2024; tetradecylpyridinium chloride (TPC);N-tetradecyl-4-ethylpyridinium chloride (TDEPC); octenidine; delmopinol,octapinol, and other piperidino derivatives; nicin preparations;zinc/stannous ion agents; antibiotics such as augmentin, amoxicillin,tetracycline, doxycycline, minocycline, and metronidazole; and analogsand salts of the above antimicrobial antiplaque agents. If present, theantimicrobial antiplaque agents generally comprise from about 0.1% toabout 5% by weight of the compositions of the present invention.

Anti-inflammatory agents may also be present in the oral compositions ofthe present invention. Such agents may include, but are not limited to,non-steroidal anti-inflammatory agents such as aspirin, ketorolac,flurbiprofen, ibuprofen, naproxen, indomethacin, aspirin, ketoprofen,piroxicam and meclofenamic acid, and mixtures thereof. If present, theanti-inflammatory agents generally comprise from about 0.001% to about5% by weight of the compositions of the present invention. Ketorolac isdescribed in U.S. Pat. No. 5,626,838, issued May 6, 1997. Both of thesereferences are incorporated herein by reference in their entirety.

Other optional agents include synthetic anionic polymericpolycarboxylates being employed in the form of their free acids orpartially or preferably fully neutralized water soluble alkali metal(e.g. potassium and preferably sodium) or ammonium salts and aredisclosed in U.S. Pat. Nos. 4,152,420 to Gaffar, 3,956,480 to Dichter etal., 4,138,477 to Gaffar, 4,183,914 to Gaffar et al., and 4,906,456 toGaffar et al. Preferred are 1:4 to 4:1 copolymers of maleic anhydride oracid with another polymerizable ethylenically unsaturated monomer,preferably methyl vinyl ether (methoxyethylene) having a molecularweight (M.W.) of about 30,000 to about 1,000,000. These copolymers areavailable for example as Gantrez (AN 139 (M.W. 500,000), A.N. 119 (M.W.250,000) and preferably S-97 Pharmaceutical Grade (M.W. 70,000), of GAFCorporation.

The present invention can also optionally comprise selective H-2antagonists including compounds disclosed in U.S. Pat. No. 5,294,433,Singer et al., issued Mar. 15, 1994, which is herein incorporated byreference in its entirety.

Composition Use

A safe and effective amount of the compositions of the present inventionand/or chlorite ion may be topically applied to the mucosal tissue ofthe oral cavity, to the gingival tissue of the oral cavity, and/or tothe surface of the teeth, for the treatment or prevention of the abovementioned diseases or conditions of the oral cavity, in severalconventional ways. For example, the gingival or mucosal tissue may berinsed with a solution (e.g., mouth rinse, mouth spray) containingchlorite ion; or if chlorite ion is included in a dentifrice (e.g.,toothpaste, tooth gel or tooth powder), the gingival/mucosal tissue orteeth is bathed in the liquid and/or lather generated by brushing theteeth. Other non-limiting examples include applying a non-abrasive gelor paste, which contains chlorite ion, directly to the gingival/mucosaltissue or to the teeth with or without an oral care appliance describedbelow; chewing gum that contains chlorite; chewing or sucking on abreath tablet or lozenge which contains chlorite ion. Preferred methodsof applying chlorite ion to the gingival/mucosal tissue and/or the teethare via rinsing with a mouth rinse solution and via brushing with adentifrice. Other methods of topically applying chlorite ion to thegingival/mucosal tissue and the surfaces of the teeth are apparent tothose skilled in the art.

The concentration of chlorite ion in the composition of the presentinvention depends on the type of composition (e.g., toothpaste, mouthrinse, lozenge, gum, etc.) used to apply the chlorite ion to thegingival/mucosal tissue and/or the teeth, due to differences inefficiency of the compositions contacting the tissue and teeth, and duealso to the amount of the composition generally used. The concentrationmay also depend on the disease or condition being treated.

It is preferred that the mouth rinse to be taken into the oral cavityhave a concentration of chlorite ion in the range of from about 0.04% toabout 0.4%, with from about 0.075% to about 0.2% more preferred and fromabout 0.1% to about 0.2%, by weight of the composition, even morepreferred. Preferably mouth rinse compositions of the present inventiondeliver 3.75 to 22.5 mg of chlorite ion to the oral cavity whenapproximately 15 ml of the rinse is used.

Mouth sprays preferably have chlorite ion concentrations from about0.15% to about 4%, with from about 0.2% to about 4% more preferred, withfrom about 0.75% to about 2%, by weight of the composition, even morepreferred.

Preferably for dentifrices (including toothpaste and tooth gels) andnon-abrasive gels, the concentration of chlorite ion is in the range offrom about 0.4% to about 4.5%, by weight of the composition, with fromabout 0.75% to about 3% preferred, and from about 1.5% to about 2%, byweight of the composition, even more preferred.

Chewing gums and lozenges (including breath mints), are generallyformulated into compositions of individual unit size preferablycontaining from about 0.1 mg to about 12 mg, preferably from about 1 mgto about 6 mg, of chlorite ion, per unit used in the oral cavity (i.e.per stick of gum, lozenge, breath mint, etc.).

For dual phase compositions the above concentrations of chlorite ionrepresent the concentration of chlorite ion after the two phases aremixed together, which is usually just prior to use by the consumer.

For the method of treating diseases or conditions of the oral cavity,including breath malodor (as well as long lasting breath protection), ofthe present invention, a safe and effective amount of chlorite ion ispreferably applied to the gingival/mucosal tissue and/or the teeth (forexample, by rinsing with a mouthrinse, directly applying a non-abrasivegel with or without a device, applying a dentifrice or a tooth gel witha toothbrush, sucking or chewing a lozenge or breathmint, etc.)preferably for at least about 10 seconds, preferably from about 20seconds to about 10 minutes, more preferably from about 30 seconds toabout 60 seconds. The method often involves expectoration of most of thecomposition following such contact. The frequency of such contact ispreferably from about once per week to about four times per day, morepreferably from about thrice per week to about three times per day, evenmore preferably from about once per day to about twice per day. Theperiod of such treatment typically ranges from about one day to alifetime. For particular oral care diseases or conditions the durationof treatment depends on the severity of the oral disease or conditionbeing treated, the particular delivery form utilized and the patient'sresponse to treatment. If delivery to the periodontal pockets isdesirable, such as with the treatment of periodontal disease, amouthrinse can be delivered to the periodontal pocket using a syringe orwater injection device. These devices are known to one skilled in theart. Devices of this type include “Water Pik” by Teledyne Corporation.After irrigating, the subject can swish the rinse in the mouth to alsocover the dorsal tongue and other gingival and mucosal surfaces. Inaddition a toothpaste, non-abrasive gel, toothgel, etc. can be brushedonto the tongue surface and other gingival and mucosal tissues of theoral cavity.

For the method of whitening teeth of the oral cavity, a safe andeffective amount of chlorite ion is preferably applied, with or withoutan oral care device such as a toothbrush, tray containing thecomposition, plastic strips (as disclosed hereinafter), etc., to thesurface of the teeth: for mouthrinses or mouthsprays and for toothpastesor tooth gels, preferably for at least about 10 seconds, preferably fromabout 20 seconds to about 10 minutes, more preferably from about 30seconds to about 60 seconds and for non-abrasive gels (applied with anappliance) preferably at least about 10 minutes to about 12 hours,preferably from about 20 seconds to about 10 minutes. The method ofteninvolves expectoration of most of the composition following suchcontact, preferably followed with rinsing, e.g. with water. Thefrequency of such contact is preferably from about once per week toabout four times per day, more preferably from about thrice per week toabout three times per day, even more preferably from about once per dayto about twice per day. The period of such treatment typically rangesfrom about one day to a lifetime. The subject may repeat the applicationas needed to whiten their teeth. The duration of treatment is preferablyfrom about 3 weeks to about 3 months, but may be shorter or longerdepending on the severity of the tooth discoloration being treated, theparticular delivery form utilized and the patient's response totreatment.

In a preferred application, the consumer applies to their teeth, a thinplastic film pre-coated with the present composition, and wears it fromabout 10 minutes to 8 hours as described above. The consumer uses a newstrip for each application of the present composition. This type ofstrip appliance is further described in P&G Copending ApplicationsSerial Nos. 08/870,664; 08/870,330; 08/870,331 and 08/870,665 all filedJun. 6, 1997, the disclosures of which are herein incorporated byreference in their entirety.

The following non-limiting examples further describe preferredembodiments within the scope of the present invention. Many variationsof these examples are possible without departing from the scope of theinvention.

All percentages used herein are by weight of the composition unlessotherwise indicated.

EXAMPLES

The following examples are made by conventional processes by mixing thefollowing:

Example 1 - Dual Phase Dentifrice Dentifrice Phase Chlorite PhaseIngredient Wt. % Ingredient Wt. % Water 20.680 Sodium Chlorite (80%)7.50 Sorbitol (70% Solution) 18.534 Carbopol 956² 5.62 Glycerin 9.000Water 83.14 Sodium Carbonate 1.000 Sodium Carbonate 0.53 Sodium Fluoride0.486 Sodium Bicarbonate 0.42 Propylene Glycol 8.000 Sodium Hydroxide2.79 Hydrated Silica 30.00 Xanthan Gum 0.500 Carboxymethyl Cellulose¹0.400 Sodium alkyl sulfate 8.000 (27.9% Sol'n) Titanium Dioxide 0.700Sodium Saccharin 0.600 Flavor 2.000 Methyl Paraben 0.070 Propyl Paraben0.030 Chlorite phase pH = 10 Total 100.00 Total 100.00 After phasesmixed in a 1:1 vol./vol. Ratio, pH approximately 8.5 to 9. ¹Grade 7M8SFfrom Aqualon. ²Available from B. F. Goodrich.

Example 2 - Dual Phase Dentifrice Dentifrice Phase Chlorite PhaseIngredient Wt. % Ingredient Wt. % Water 22.180 Sodium Chlorite (80%)2.50 Sorbitol (70% Solution) 13.534 Carbopol 956² 3.72 Glycerin 9.000Water 91.07 Disodium Phosphate 4.500 Sodium Carbonate 0.53 SodiumFluoride 0.486 Sodium Bicarbonate 0.42 Propylene Glycol 8.000 SodiumHydroxide 1.76 Hydrated Silica 30.00 Xanthan Gum 0.500 Carboxymethyl0.400 Cellulose¹ Sodium alkyl sulfate 8.000 (27.9% Sol'n) TitaniumDioxide 0.700 Sodium Saccharin 0.600 Flavor 2.000 Methyl Paraben 0.070Propyl Paraben 0.030 Chlorite phase pH = 10 Total 100.00 Total 100.00After phases mixed in a 1:1 vol./vol. Ratio, pH approximately 7.5.¹Grade 7M8SF from Aqualon. ²Available from B. F. Goodrich.

Example 3 - Single Phase Dentifrice Ingredient Wt. % Water 62.277 SodiumChlorite 3.750 Sodium Fluoride 0.243 Hydrated Silica 25.000 Xanthan Gum0.600 Carbomer 956¹ 0.200 Sodium alkyl 4.000 sulfate (27.9% Sol'n)Titanium Dioxide 1.000 Sodium Saccharin 0.130 Flavor 1.000 SodiumHydroxide 1.800 (50% Sol'n) Total 100.00 ¹Available from B. F. Goodrich.pH approximately 10.

Example 4 - Dual Phase Mouthwash Mouthwash Phase Chlorite PhaseIngredient Wt. % Ingredient Wt. % Water 45.00 Sodium Chlorite (80%) 0.25Glycerin 19.24 Water 98.80 Sodium Bicarbonate 1.00 Sodium Carbonate 0.53Poloxamer 407 0.80 Sodium Bicarbonate 0.42 Polysorbate 80 0.20 SodiumSaccharin 0.20 Flavor 0.50 Color 0.06 Alcohol 33.00 pH = 10 Total 100.00Total 100.00

Example 5 - Single Phase Mouthwash Ingredient Wt. % Water 98.80 SodiumChlorite 0.25 Sodium Carbonate 0.53 Sodium Bicarbonate 0.42 Total 100.00

Example 6 - Chlorite Lozenge Ingredient Na Chlorite 6 mg. Per lozengeFlavor As desired Magnesium Stearate 7.5 mg. Stearic Acid 75 mg.Compressible Sugar QS 1500 mg.

Example 7 Dry Powder Mouthrinse for Reconstitution Ingredient Weight %Spray Dried Ethanol¹ 85.38 Sodium Bicarbonate 5.34 Sodium Chlorite (80%)1.60 Tastemaker Spray Dried Spearmint #214487 6.40 Aspartame 0.43Acesulfame Potassium 0.85 Total 100.00 ¹30% load, available fromTakasago.

Example 8 Dry Powder Mouthrinse for Reconstitution Ingredient Weight %Spray Dried Ethanol¹ 75.00 Sodium Bicarbonate 15.72 Sodium Chlorite(80%) 1.60 Tastemaker Spray Dried Spearmint #214487 6.40 Aspartame 0.43Acesulfame Potassium 0.85 Total 100.00 ¹30% load, available fromTakasago.

Add dry ingredients, listed above, in any order, and mix until achievinga homogeneous mixture. Colorants, to provide color after adding water tothe dry mixture, are optional.

To make finished mouthwash

Example 7: Add 1.874 grams of dry powder blend to 15 ml. of H₂O in asmall dose cup with lid. Shake vigorously until solids dissolve, rinseand expectorate.

Example 8: Add 1.874 grams of dry powder blend to 15 ml. of H₂O in smalldose cup with lid. Shake vigorously until solids dissolve, rinse andexpectorate.

Example 9 Non-Abrasive Gel Ingredient Weight % Sodium Chlorite (80%)3.75 Carbopol 956¹ 8.00 Sodium Bicarbonate 0.84 Sodium Hydroxide (50%Solution) 8.00 (approx. sufficient to get pH 10) Water QS 100%¹Available from B. F. Goodrich.

Example 10 Non-Abrasive Gel Ingredient Weight % Sodium Chlorite (80%)3.18 Carbopol 956¹ 3.90 Sodium Bicarbonate 0.84 Sodium Hydroxide (50%Solution) 3.90 (approx. sufficient to get pH 10) Water QS 100%¹Available from B. F. Goodrich.

For Examples 9 and 10, disperse the Carbopol in water. Thereafter, addthe sodium hydroxide and mix. Then add the sodium bicarbonate and mix.Check the pH and adjust to pH of 10 with sodium hydroxide, if needed.Finally, add the sodium chlorite and mix.

What is claimed is:
 1. A toothpaste composition comprising a first and asecond phase: (a) the first phase comprising greater than about 0.2% byweight of the final composition, of chlorite ion from chlorite salts;and (b) the second phase comprising a pharmaceutically-acceptabletopical, toothpaste oral carrier containing no chlorite ion; wherein thepH of the final composition is greater than 7.5 and wherein the level ofchlorine dioxide or chlorous acid in the final composition is less thanabout 50 ppm.
 2. The composition of claim 1 wherein the compositioncomprises greater than about 0.4%, by weight of the composition ofchlorite ion.
 3. The composition of claim 1 wherein the compositioncomprises greater than about 0.75%, by weight of the composition, ofchlorite ion.
 4. The composition of claim 1 wherein the level ofchlorine dioxide and chlorous acid in the final composition is less thanabout 10 ppm.
 5. The composition according to claim 1 wherein the finalcomposition is essentially free of chlorine dioxide and chlorous acid.6. The composition according to claim 1 wherein saidpharmaceutically-acceptable oral carrier comprises components selectedfrom the group consisting of a flavorant, surfactant, fluoride ion,abrasive, and mixtures thereof.
 7. The composition according to claim 6,wherein the pharmaceutically-acceptable topical oral carrier comprisesfluoride ion at a level from about 0.05% to about 0.3% by weight of thefinal composition.
 8. An oral care non-abrasive gel compositioncomprising a first and a second phase: (a) the first phase comprisinggreater than about 0.2% by weight of the final composition, of chloriteion from chlorite salts; and (b) the second phase comprising apharmaceutically-acceptable topical, gel composition oral carriercontaining no chlorite ion; wherein the pH of the final composition isgreater than 7.5 and wherein the level of chlorine dioxide or chlorousacid in the final composition is less than about 50 ppm.
 9. Thecomposition of claim 8 wherein the composition comprises greater thanabout 0.4%, by weight of the composition of chlorite ion.
 10. Thecomposition of claim 9 wherein the composition comprises greater thanabout 0.75%, by weight of the composition, of chlorite ion.
 11. Thecomposition of claim 10 wherein the level of chlorine dioxide andchlorous acid in the final composition is less than about 10 ppm. 12.The composition according to claim 10 wherein the final composition isessentially free of chlorine dioxide and chlorous acid.
 13. Thecomposition according to claim 10 wherein saidpharmaceutically-acceptable oral carrier comprises components selectedfrom the group consisting of a flavorant, surfactant, fluoride ion,abrasive, and mixtures thereof.
 14. The composition according to claim13, wherein the pharmaceutically-acceptable topical oral carriercomprises fluoride ion at a level from about 0.05% to about 0.3% byweight of the final composition.
 15. A toothpaste composition comprisinga first and a second phase: (a) the first phase comprising greater thanabout 0.2% by weight of the final composition, of chlorite ion; and (b)the second phase comprising from about 0.05% to about 0.3%, by weight ofthe final composition, fluoride ion in a pharmaceutically-acceptabletopical, toothpaste oral carrier and comprising no chlorite ion; whereinthe pH of the final composition is greater than 7.5.
 16. The toothpastecomposition according to claim 15 wherein the fluoride ion concentrationin the composition is from about 50 ppm to about 3500 ppm.
 17. Thetoothpaste composition according to claim 15 wherein the fluoride ionconcentration in the composition is from about 500 ppm to about 3000ppm.
 18. A method for the treatment or prevention of breath malodor, byadministering to the oral cavity, the oral care toothpaste compositionaccording to claim
 1. 19. A method for the treatment or prevention ofbreath malodor, by administering to the oral cavity, the oral carenon-abrasive gel composition according to claim
 8. 20. A method for thetreatment or prevention of breath malodor, by administering to the oralcavity, the oral care non-abrasive gel composition according to claim15.